Introduction: Between May and September 2016, four cases of tuberculosis were reported at various Tuberculosis Control Centers (CLATs) in Aquitaine. Upon interviewing the patients, it became apparent that they all attended the same high school in the Pyrénées-Atlantiques department. A screening of the primary contacts, later expanded to include secondary contacts, was organized; this screening was then repeated six months later following the diagnosis of new cases in the community. This article describes the organization, results, and challenges of this large-scale investigation into a cluster of tuberculosis cases at a high school in 2016–2017. Methods: Screening was conducted in accordance with the recommendations of the High Council for Public Health, either at the Clat or on-site for expanded screenings. A second expanded screening was conducted on-site six months later. Results: Screening of 2,804 individuals led to the diagnosis of 9 cases of tuberculosis, almost all of whom were carriers of the same strain of Mycobacterium tuberculosis. A total of 13 cases of tuberculosis occurred at the high school. In addition, 218 latent tuberculosis infections (LTIs) were diagnosed. The highest rates of LTI were observed among boarding students and in certain classes. Discussion: This outbreak was facilitated by the vulnerability of these young adult populations and their lifestyle. The spread of this outbreak would have continued had these two expanded screenings, covering the entire high school, not been conducted. These efforts helped stop the outbreak, first by diagnosing 6 silent tuberculosis cases that had not yet produced any clinical symptoms, and second by treating the LTI cases. This investigation would not have been possible without the mobilization and collaboration of all stakeholders on the ground and public health authorities, working together in a multidisciplinary approach that fostered critical thinking. The Clat’s networked approach enabled the rapid identification of these clustered cases and has proven to be very important for regional surveillance.